Several problems related to viral tumorigenesis will be studied. 1) SV40 early genes and regulatory signals will be characterized by use of constructed deletion and point mutants and by nucleotide sequence analysis. 2) SV40-cell DNA junctions from variants and from transformed cells will be characterized by nucleotide sequence analysis. 3) SV40 DNA will be compared with that of other primate papovaviruses. 4) Adenovirus DNA replication will be studied by electron microscopy, using ts mutants. 5) Additional mutants for enzymes involved in repair will be isolated from E. coli, including multiple mutants, in order to isolate and characterize intermediates in repair. 6) The endonucleolytic activity of exonuclease III will be characterized further. 7) Recombination mechanisms will be explored in Hemophilus, particularly the possible role of exonuclease V. 8) Recognition of nucleotide sequences by restriction endonucleases and modification methylase will be further defined and the properties of the enzymes studied in detail. 9) SV40-DNA recombinants will be studied to determine the expression of inserted genes. BIBLIOGRAPHIC REFERENCES: Rundell, Kathleen, Collins, John K., Tegtmeyer, Peter, Ozer, Harvey L., Lai, Ching-Juh, and Nathans, Daniel (1977). Identification of simian virus 40 protein A. J. Virol. 21:636-646. Scott, Walter A., Brockman, William W., and Nathans, Daniel (1976). Biological activities of deletion mutants of simian virus 40. Virology 75:319-334.